Background Achieving sustained remission is nowadays a realistic treatment goal in patients with rheumatoid arthritis (RA). However, the effect of methotrexate (MTX) on sustained remission in treatment with adalimumab and etanercept on long term is not yet clear.
Objectives To investigate the effect of MTX use on clinical response in RA patients treated with adalimumab or etanercept during 2 years of follow-up.
Methods Patients treated with adalimumab or etanercept were consecutively included in a one-center prospective observational cohort. If patients used both biologicals, only the first biological was used in this study. Follow-up was 2 years with scheduled visits at baseline and 4, 16, 28, 40, 52, 78 and 104 weeks thereafter. The choice of biological was determined by the treating rheumatologist. Outcome measurements were: sustained remission (which was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for at least 24 consecutive weeks), drug discontinuation, and the improvement on Health Assessment Questionnaire (HAQ) and DAS28 compared to baseline. An independent t-test, chi-square test and cox regression analysis were used to compare outcomes between patients treated with and without MTX in both etanercept and adalimumab treatment.
Results Four hundred twenty-nine patients (48%) were treated with adalimumab (of which 77% used concomitant MTX) and 457 patients (52%) with etanercept (of which 68% used concomitant MTX). For adalimumab, hazard ratio (HR) to achieve sustained remission was 2.3 (95% confidence interval (CI) [1.4-3.9], p=0.001) for patients treated with MTX versus without. For etanercept, HR was 1.1 (95% CI [0.8-1.6], p=0.535), see figure. For adalimumab, more patients treated with MTX achieved sustained remission than patients without (respectively; 42% vs. 18%; p<0.001) and no significant difference was found for etanercept (with MTX 33% vs. without MTX 28%; p=0.245). Fifty-six percent of patients treated without MTX discontinued adalimumab versus 31% of patients treated with MTX (p<0.001). For etanercept, the discontinuation rate was 48% of patients treated without MTX versus 36% of patients with MTX (p=0.015). ΔHAQ and ΔDAS28 were not significantly different between patients with and without MTX for both adalimumab and etanercept at all time-points except at 4 weeks (ΔDAS28 was higher for adalimumab in patients with MTX versus without).
Conclusions This is the first long term study focusing on the effect of MTX use on sustained remission for adalimumab and etanercept. We found that RA patients using MTX are more likely to achieve sustained remission during adalimumab treatment, however, for etanercept this difference was not found. Patients treated with MTX have a lower risk of discontinuation in both etanercept and adalimumab treatment.
Disclosure of Interest M. l'Ami: None declared, E. Kneepkens Speakers bureau: Pfizer, C. Krieckaert: None declared, A. Marsman: None declared, J. Ruwaard: None declared, G. Wolbink Grant/research support from: Pfizer, Speakers bureau: Pfizer, Amgen, M. Nurmohamed Grant/research support from: AbbVie, BMS, Pfizer, UCB, Roche, Consultant for: Abbot, BMS, Pfizer, Roche, Speakers bureau: AbbVie, Pfizer, Roche